Origin of blood cells Flashcards

1
Q

What is haematopoiesis

A

the commitment and differentiation processes that lead to the formation of all blood cells from haematopoietic stem cells

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2
Q

What is the stem cell lineage

A
  1. Stem cells
  2. Early progenitors
  3. Late progenitors
  4. Immature precursors
  5. Mature cells
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3
Q

What are key rules when it comes to stem cell lineage

A

The mature cells cannot go back to being stem cells
Only stem cells can divide to produce more stem cells
Progenitor cells are differentiated from stem cells but this cannot be seen through a microscope

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4
Q

Where does haematopoiesis occur in an early embryo

A

The yolk sac

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5
Q

Where does haematopoiesis occur in a foetus

A

The foetal liver

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6
Q

Where does haematopoiesis occur in an infant

A

Through the bone marrow

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7
Q

Where does haematopoiesis occur in an adult

A

The central skeleton (vertebrae, ribs and sternum, skull, sacrum, pelvis and the proximal end of the humerus and femur)

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8
Q

Whats red marrow

A

Active haematopoiesis

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9
Q

What yellow marrow

A

Filled with fat cells

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10
Q

What does a blood marrow trephine do and how is it performed

A

Its used to examine bone marrow architecture

remove a 1 or 2cm core of bone marrow in one piece

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11
Q

What is a bone marrow aspiration

A

sucks some bone marrow cells up into a syringe

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12
Q

What is the neutrophil lineage - myelopoiesis

A
  1. Myeloblast
  2. Promyelocyte
  3. Myelocyte
  4. Metamyelocyte
  5. Band
  6. Segmented neutrophil
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13
Q

What is the red blood cell lineage - erythropoiesis

A
  1. Pro-erythroblast
  2. Basophilic erythroblast
  3. Polychromatic erythroblast
  4. Pyknotic erythroblast
  5. Reticulocyte
  6. Mature red blood cell
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14
Q

Platelet formation

A
  1. Megakaryoblast - DNA replication but no cell division
  2. Megakaryocyte - Large, polypoid cell
  3. Blood platelets - cytoplasmic fragments
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15
Q

Lymphopoiesis

A
  1. Stem cell
  2. Common lymphoid progenitor
  3. T-lymphocytes and B-lymphocytes
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16
Q

T-cell formation in thymus

A
  1. Early progenitor migrates to thymus
  2. T-cell receptor gene rearrangement to get necessary antibodies
  3. Positive and negative selection to prevent auto immunity
17
Q

B-cell formation in bone marrow

A
  1. immunoglobin gene rearrangment
  2. Expression of surface IgM
  3. Immature B-cell migrates to secondary lymphoid organs for maturation and antigen selection
18
Q

How are progenitors undifferentiated

A

You cannot tell the difference between them morphologically because they do not show the characteristics of mature cells

19
Q

How are progenitors committed

A

They are already committed as to what they will become when they generate mature cells

20
Q

How do you form colonies

A
  • Semi-solid medium
  • Plus growth factors
  • Single cell suspension of bone marrow
  • Will form colonies
21
Q

What colonies will progenitors form

A

Colonies of mature cells

Thus progenitors are called ‘colony forming units’ (CFU)

22
Q

What colonies will early erythroid progenitors form

A

They will form ‘burst forming unit - erythroid’ (BFU-E)

23
Q

What are CSF

A

Colony stimulating factors

24
Q

How is a bone marrow transplant done

A
  1. Completely ablate haemopoiesis with radiation and drugs
  2. Infuse compatible donor bone marrow cells
  3. Haemopoiesis can be completely restored
25
Q

What must bone marrow donors be

A

Must be HLA matched; sibling or unrelated donor

Or autologous BMT; Re-infuse patients own bone marrow

26
Q

What are the applications of bone marrow transplant

A
  1. Leukaemia, lymphoma and myeloma
  2. Intensified chemotherapy
  3. Genetic diseases e.g. SCID, thalassaemia
27
Q

What are the risks of a bone marrow transplant

A
  • Significant mortality whilst waiting for engraftment
  • Infection due to neutropenia (low neutrophil count)
  • Bleeding
  • Graft versus host disease (GVHD)
28
Q

What are the benefits of of a bone marrow transplant

A

For many diseases this is the only curative treatment

29
Q

How can stem cells be studied through mice

A
  1. Mark stem cells by retrovirus insertion
  2. Transplant irradiated mice with small number of stem cells
  3. Same marked stem cells gives rise to neutrophils and lymphocytes
30
Q

How can stem cells be studied through humans

A
  1. Chronic myeloid leukaemia (CML) is caused by a chromosome translocation in stem cells
  2. provides a natural marker within cells
  3. The disease mostly effects neutrophil lineage, but Philadelphia chromosome also found in T-lymphocytes and other lineages
31
Q

What are growth factors and how do they work

A

Polypeptide growth factors
Bind to cell surface transmembrane receptors
Stimulates growth and survival of progenitors

32
Q

Where and why is erythropoietin produced and what does it do

A

Produced in the kidney is response to hypoxia

Increases red blood cell production by increasing survival of erythroid progenitors (CFU-E)

33
Q

What is the clinical application of recombinant erythropoietin

A

Treating anaemia of kidney failure, alternative to blood transfusion in Jehovahs witnesses

34
Q

Where is granulocyte colony stimulating factor (G-CSF) produced, why and what does it do

A

Produced by many cell types in response to inflammation
Its a glycoprotein that stimulates the bone marrow to produce neutrophils and neutrophil progenitors and release them into the bloodstream

35
Q

What are the clinical applications of G-CSF

A

Stimulate neutrophil recovery after bone marrow transplantation and chemotherapy
Treatment of neutropenia
Treatment is seemed to be working after appearance of CD34